Lab Soft News

The Metabolic Syndrome: Risk Factors and Diagnosis

I have been intrigued by the recent surge of interest in the metabolic syndrome, which is characterized by a group of so-called metabolic risk factors in one person. They include, according to an American Heart Association article posted on the web (see: Metabolic Syndrome), the following:

• Abdominal obesity
• Atherogenic dyslipidemia
• Elevated blood pressure
• Insulin resistance or glucose intolerance
• Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood)
  
• Proinflammatory state (e.g., elevated C-reactive protein in the blood)
  

People with the metabolic syndrome are at increased risk for coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease) and type 2 diabetes. The metabolic syndrome has become increasingly common in the United States. It’s estimated that over 50 million Americans currently have it. It's diagnosed by the presence of three or more of the following:

• Elevated waist circumference
• Elevated triglycerides
• Reduced HDL cholesterol
• Elevated blood pressure
• Elevated fasting glucose

Apropos of the  diagnosis of metabolic syndrome, I came across a recent research report that may have some relevance for this topic (see: Vitamin A protein may reveal hidden body fat). Below is an excerpt from it (boldface emphasis mine):

Measuring blood levels of a chemical transporter for vitamin A may be useful in estimating a person's "intraabdominal fat," a type of fat inside the abdomen that it not visible, but still adversely affects health, new research shows. In addition, measuring levels of this chemical transporter, called retinol-binding protein (RBP4), may help identify patients with insulin resistance, a disturbance in sugar metabolism associated with the development of type 2 diabetes, according to a report in the journal Cell Metabolism....In fact, RBP4 was a better predictor of intraabdominal fat and insulin resistance than several other blood tests that were evaluated

Given the prevalence of this syndrome and the criticality of lab tests for its diagnosis, the metabolic syndrome needs to be part of the vocabulary of all lab professionals.

In-Vivo/In-Vitro Diagnostics and the National Reference Labs

I have begun to use the term in-vitro/in-vivo diagnostics (IV2D) to refer to the blending, or even merger, of the clinical labs, pathology, and radiology. The ultimate goal of such an organizational change would be to facilitate the emergence of a new breed of specialist, the diagnostic hybridist, to diagnose disease, assess the prognosis of disease, and assist clinicians in their choice of therapy. I will take the term IV2D to encompass what I have referred to in previous notes as the early health model and also full service diagnostics.

One of the major competitive challenges to the hospital clinical labs and pathology services has been the large national reference labs. One of the competitive advantages of the hospital-based labs has been the ready access of the hospital-based professionals working in such labs to patients' EMRs. When I first began to analyze the implications of the early health model, I wondered whether such an approach to healthcare would favor the national reference labs. Such an advantage could occur because the early health model is based on the diagnosis of pre-clinical/pre-symptomatic disease. Such an approach could make access to the patients' EMR less important because the patients' signs and symptoms, as documented in the EMR, become less relevant.

Even though the early health model is an integral component of IV2D, my concerns about the competitive challenge of the national reference labs have diminished for the following reason. IV2D, if and when properly executed, requires tight collaboration between pathology, molecular diagnostics, the radiology department, and the clinicians caring for patients. Such collaboration would be required from the time that, for example, a tumor is diagnosed at an early stage by the presence of an abnormal serum biomarker profile until the tumor is removed and the neoplastic tissue analyzed. I suspect that the remotely located national reference labs would have difficulty executing the necessary series of hand-offs to coordinate such processes. If the truth be told, I suspect that most hospital-based units would also be unable, at present, to execute such hand-offs. However, I am hoping that they will be able to do so in the future, perhaps assisted by specialized work-flow software. Their physical proximity in hospitals should facilitate this learning process.

Eight Tips for How Money CAN Buy you Happiness.

This is a bonus posting unrelated to my normal material that I have copied from another site  -- The Happiness Project. It's so good I wanted to share it with my readers.

1. Strengthen bonds with family and friends. Studies show that having close relationships is one of the most important elements of a happy life.
2. End marital conflict. If you’re constantly arguing about the unkempt lawn, or the moldering laundry, see if you can throw some money at the problem. Can you hire the teenager down the street to clean out the garage?
3. Upgrade your exercise. Studies show that one of the quickest and surest ways to boost your mood is to exercise. If spending money on a new iPod, a more convenient gym, or a new pair of yoga pants will make it easier to get yourself off the couch, that's a good happiness investment.
4. Think about fun. Ask yourself – and be honest – what’s fun for you?... For happiness, you’re better off using your money to have a great experience than to gain a possession.
5. Serenity and security. Peace of mind is critical to happiness, so use the money to pay down your debts or to add to your savings.
6. Pay more for healthy food. It’s a sad fact that fruits, vegetables, and healthy food are more expensive than fast food, but eating healthfully will pay off in the long run, in terms of your good health and energy.
7. Spend the money on someone else. One of the best ways to make yourself happy is to make someone else happy. Think about ways you could spend the money that would make a big difference to someone else -- whether someone you know, or a cause you support.
8. Think about YOUR priorities....So maybe that fancy new TV set would mean a lot to you, although I, for one, would hardly notice the difference. As always, the key to any happiness question is to know yourself, and what makes YOU happy.

Are We Ready for the Diagnostic Hybridist?

As veteran readers of Lab Soft News may know, I have developed a special interest in the conversion or merger of pathology, lab medicine, and radiology with the eventual [potential] outcome of a "Department of Diagnostic Medicine." I have been struggling in my various notes to come up with a good name for this concept and have finally settled on in-vivo/in-vitro diagnostics which I will refer to here using the acronym IV2DM.

The July issue of CAP Today discussed this idea in its cover story. You can link to the story as a PDF file (see: In diagnoses, a tale of two specialties) or in text format at the CAP Today web site. For me, the significance of this article is twofold. First of all, it's important that one of the CAP most respected publications is giving such prominence to this idea. The second important point that is emphasized in the article is that the Methodist Hospital in Houston is exploring this idea in depth through its research arm, The Methodist Hospital Research Institute (TMHRI).

One of the most intriguing aspects of IV2D for me is the means by which it will evolve in the two specialties and the workplace. In other words, how and where will the idea take root and flourish? The money quote from the CAP Today article was the following (boldface emphasis mine):

“I think what’s going to happen is that two or more smart people with a particular interest around a specific topic are going to talk,” says Dr. [James] Musser, associate chair, Department of Pathology, The Methodist Hospital, and executive vice president of the Research Institute. “They’re going to start formulating specific ideas. It could be, for example, liver pathology or infectious disease. I don’t think we know where the solutions are going to come from. I think much of this is going to be driven very much at the grass-roots level, in my opinion, by two or more individuals who have a shared passion over some medical problem or biomedical problem. And that’s how this synthesis of fields is going to move forward.” On a practice level, Dr. Musser foresees “a hybrid field filled with hybrid individuals,” much like what has happened in molecular pathology. “Now we have training programs in molecular and so forth, and a society and journals, and it’s a viable academic enterprise. Hybrid vigor is crucial to the ongoing success of any discipline,” he adds, including medicine.“If fields don’t mutate they die.”

I believe that Dr. Musser is right on target here on a couple of counts. IV2D will surely evolve from the bottom up rather than emerge fully formed in some healthcare setting.  This evolutionary process will be driven by local partnerships to demonstrate the power of combining in-vivo and in-vitro diagnosis. I am also struck by the aptness of his reference to  "hybrid vigor." Perhaps the label of diagnostic hybridist will find favor among the practitioners of this new specialty, much like the intensivist, hospitalist, surgicalist, and proceduralist.

Investors Put Beckman Coulter into Play after Siemens' Bid for Dade

I covered yesterday the Siemens bid for Dade (see: Siemens to Acquire Dade Behring for $7 Billion). This has caused an increased interest in Beckman Coulter with GE highlighted as a potential purchaser (see: Siemens to Buy Dade, Fueling Hopes For Beckman Bid). Below is an excerpt from an excellent article published yesterday discussing this possibility (boldface emphasis mine):

The $6.3 billion takeover bid for Dade Behring Holdings by Siemens, the latest deal in the hot clinical diagnostic business, is lifting shares of Dade rival Beckman Coulter mid expectations it too will get an offer, analysts said on Wednesday....Dade's deal with German industrial conglomerate Siemens is worth $77 per share, a 38 percent premium over Tuesday's closing price. Analysts said the large premium was causing investors to see Beckman Coulter as an acquisition target....[An analyst] said Dade's Vista technology gave it an advantage over Beckman Coulter in Siemens' eyes. The diagnostic tests are used widely in smaller-volume laboratories. "Soon there will be no pure plays left in diagnostics," [an anslyst] said. "Beckman Coulter is the last pure play in the diagnostic business. The pool is shrinking for potential buyers."...Siemens has about 12 percent of the market, he said, while Dade and Beckman each have about 11 percent to 12 percent. Roche has about 18 percent....Earlier this month, General Electric Co. (GE) acknowledged that it would continue to seek acquisitions in the diagnostic sector after terminating an $8.1 billion deal to buy two such businesses from Abbott. The parties scrapped the deal as they could not agree on terms.

Five Alternative IVD + Software Business Models

I attended a presentation at the recent AACC annual conference in San Diego entitled Integrating Laboratory Diagnostics and Diagnostic Imaging by an IT-Driven Environment. One of the four speakers in this session was Emery Stephens, president of Enterprise Analysis Corporation (EAC), a noted lab consultant. His excellent lecture was entitled Health Care Information Technology in Transition. Click on this link to view his entire presentation. Inspired by his slide #7 and drawing heavily on its content, I decided to explore five alternative business models that combine variations on in-vitro diagnostics with lab/medical software. I list them below in an attempt to develop a better understanding of the future direction of the lab software industry. My goal in this note is only to list the models and then discuss them in detail at some later time.

• In-vitro diagnostics + medical imaging. This model will be instantly recognizable as the current GE/Siemens approach. Both companies were competitors on a global basis for medical imaging equipment and came to the near-simultaneous conclusion that medical imaging was highly synergistic with in-vitro testing.  This approach combines in-vitro with in-vivo diagnostics. As I have noted in a previous note (see: The Pursuit of a Federated EMR Architecture by Hospital EMR Vendors), one would expect the medical software that they develop and market to support and enhance such a diagnostic-centric view of healthcare delivery.
• In-vitro diagnostics + pharmaceuticals. This is the model being pursued by Roche. Although the company is a leader in terms of its IVD products, it understands that much of its future lies in the synergy between newly emerging drugs and the companion diagnostics that will be required for an individual patient to be considered a candidate for their use (see: More Speculation About the Roche Bid for Ventana). Up to this time, Roche's interest in lab software has been limited to middleware modules that enhance and support their analyzers and reagents.
• LIS software + upstream IVD instruments. The is largely an undeveloped area but one that is theoretically possible. The only current example I would think of is Cerner's relationship to Correlagen (see: Cerner Exclusive Distributor for Correlagen's GeneExplorer). As noted in the title, this is an example of LIS software vendors reaching upstream to analyzers as opposed to the more common example of IVD vendors reaching downstream to software.
• National reference lab + lab portal software + personalized testing. The obvious example here is Quest Diagnostics and their Care360 product that was developed by their company, MedPlus. This product is a web-enabled, order-entry, results reporting link for physician offices. Their software product thus supports their core mission which is that of a large national reference lab serving physician offices. I have previously covered Quest's purchase of a company that manufactures a self-administered test for occult blood in the stool, the personalized component testing referred to above. (see: Quest Acquires Enterix).
  
• Home lab testing + home monitoring software. For this category, I have deviated somewhat from Emery's example of what he describes as decentralized rapid diagnostic testing, using Philips as an example. I have previously discussed the interest of Philips in home health monitoring in a previous note (see: Philips' Healthcare Expansion Strategy Revealed). Such an interest in home monitoring could easily be expanded to encompass home lab testing.

FDA Issues Second Draft Version of IVDMIA Guidance

The FDA Law Blog of Hyman, Phelps & McNamara provides an analysis of the second draft version of IVDMIA guidance by the FDA. I have addressed IVDMIAs in detail in multiple previous notes. I quote from the FDA Law Blog note in part below. 

FDA has released a new draft guidance for In Vitro Diagnostic Multivariate Index Assays (“IVDMIAs”).  The first version, which was released on September 7, 2006, attracted many critical comments.  The new draft seeks to address some (but not all) of those concerns.

Creating a new classification of devices called IVDMIAs, FDA is seeking to regulate a subset of laboratory developed tests.   Even though they would not be sold outside of a single laboratory, IVDMIAs would be subject to the full device regulatory scheme, including the need for FDA clearance or approval.

One of the major criticisms of the first draft was that the definition of an IVDMIA was not clear.  The proposed definition has been modified.  An IVDMIA is now defined as a device that:

1)  Combines the values of multiple variables using an interpretation function to yield a single, patient-specific result (e.g., a “classification,” “score,” “index,” etc.), that is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease, and

2)  Provides a result whose derivation is non-transparent and cannot be independently derived or verified by the end user.

The second prong of the definition is likely to attract the most attention, since it will not always be clear whether a result is “non-transparent” or how the phrase “cannot be independently derived or verified” will be applied.  FDA has given some examples of tests that are IVDMIAs, and some that are not.  These illustrations provide some greater clarity, but even so there will almost certainly be controversy over whether a particular test falls inside or outside the IVDMIA definition.

Another area of concern for commenters related to the scope of the IVDMIA “device.”  Was the device the algorithm; the algorithm and software; the algorithm, software, and laboratory tests; or something else?  FDA has definitively answered that question, although not in a way that will satisfy those who proposed a narrow definition.  The new draft guidance states:

FDA believes that any safety and effectiveness determinations that are part of the premarket review process should include review of the performance of the entire system, including the accurate measurement of the input variables, directions for use, and expected analytical or clinical performance, rather than a review of only certain subcomponents of the test.

Siemens to Acquire Dade Behring for $7 Billion

Breaking news. Siemens make a bid to acquire Dade Behring (see: Siemens to buy Dade Behring for $7 billion). Below is an excerpt from the report (boldface emphasis mine):

German clinical diagnostics company Siemens said it will buy Deerfield-based Dade Behring Holdings Inc. for $77 a share in cash or $7 billion. Munich-based Siemens, a diversified diagnostic company, will acquire Dade, which is known largely for its clinical lab tests. The companies said following the completion of the tender offer, the parties will cause a subsidiary of Siemens to merge with Dade Behring. The deal is expected to close within three to six months. Combined, Dade Behring and Siemens will have the potential to become uniquely positioned as the largest provider of clinical diagnostic products and services in the world," said Jim Reid-Anderson, chairman, president and CEO of Dade Behring.

IVD Companies as Consultants to the Clinical Labs

In a note last week (see: Several Views of “Workflow” in the Clinical Labs), I made passing mention of the fact that many IVD companies now offer Lean/Six Sigma consulting services to laboratory clients.  It occurred to me that this line of business for the IVDs may be only the opening salvo in the shift of some of them to an increased emphasis on a larger repertoire of consulting services. This is in contrast to their historical emphasis on tangible products such as analyzers and reagents rather than services. In other words, I believe that an increasing share of the revenue of the IVDs may be derived from consulting services going beyond Lean/Six Sigma.

An important question at this point what type of consulting services would such companies offer to hospital lab clients. It seems to me that there are two major reasons why Lean/Six Sigma consulting has gained traction with clinical lab managers. The first is that this topic has become so faddish that not having an ongoing a program casts doubt on the competency of lab managers. The second reason is that the value proposition presented to potential clients by Lean-Six Sigma consultants is that the ROI of the engagement is very favorable. Post-engagement, a failure to achieve the "promised" ROI can always be blamed on the client for not executing the plan well.

The type of consulting services that might be offered to clinical labs beyond Lean/Six Sigma by the IVD companies seems obvious to me. Let's define a Lean/Six Sigma engagement as focusing on lab workflow or process improvement. The next logical step to increase the quality of a lab would be to focus on the lab's functional capacity. Let's define this term as the work output of the automated instruments in the lab as well as all software such as the LIS, the lab portal system, and middleware. The goal of such a consultancy would be to improve this functional capacity measured by parameters such as an increased number of test results per day, a lower cost per test, a reduced test TAT, a broader test menu, and increased satisfaction on the part of the clinicians being served by the labs.

The Pursuit of a Federated EMR Architecture by Hospital EMR Vendors

I have discussed the federated architecture for hospital EMRs in previous notes. I believe that the current hospital EMR architecture, adopted by virtually all vendors, will be eventually unable to accommodate to the increasingly complex information being generated in radiology, pathology, and the clinical labs. Under a federated architecture, these departments will be allocated their own space in hospital EMRs, allowing the content experts in them to populate it with the information that they generate and that they are the most skilled in formatting. This will avoid the current restrictions being placed on the diagnostic information being replicated to the EMRs.

I have little expectation that EMR vendors such as Cerner would adopt such a federated model for their EMR products because to do so would highlight the deficiencies of the current systems. In addition, I also think their underlying philosophy is that the ancillary systems, and the information that they generate, need to adapt to the constraints and rules of the EMR. Put another way, I think that these companies view the "ancillary" information systems as feeders of the higher level and integrated EMR. I personally view the LIS, the RIS, and the hospital EMR as peer systems.

Interestingly and in contrast, EMR vendors such as GE and Siemens have now unveiled a much different healthcare strategy and philosophy than Cerner. Both companies are now on record as pursuing what I will call a "diagnostic-centric" vision for healthcare delivery. Siemens refers to this approach as a full service diagnostic model and GE refers to it as an early health model. In the long run, neither company will  benefit from developing and selling an EMR that places significant constraints on the major diagnostic information systems, the LIS and the RIS.

I think that it would be in the best interests of both of these companies to begin to develop an EMR based on a federated architecture. After several years in a development phase, such a system could be sold to those hospitals that place a high premium on the reporting of complex diagnostic information to their clinicians. If they truly believe that the "center of gravity" in healthcare delivery is moving toward the major diagnostic departments (i.e., pathology, clinical pathology, and radiology), their EMR philosophy and architecture should be modified to reinforce this business model.